TW200927109A - Anhydrous compositions useful for attaining enhanced sexual wellness - Google Patents

Abstract

The invention relates to an anhydrous compositeon comprising a vasodilator and an acceptable carrier wherein the vasodilator is present in an amount effective to increase the blood flow when the compositeon is applied to human tissue. The compositions according to the invention are non-flushing.

Description

200927109 VI. Description of the invention: [Technical field to which the invention belongs] This application claims to apply for the U.S. Provisional Application No. 6G/957, G87, which is filed on August 21, 2013. The present invention is hereby incorporated by reference. Related applications include U.S. Patent Application Serial Nos. 11/842,487 and No. 11/842,271, the disclosures of each of each of ❹ 10 15 ❹ 20 [Prior Art] It is estimated that there are about 4% female experience in some periods in the life of a female student. Female sexual distress disorders include complications associated with arousal, desire, or sexual intercourse that causes pain. Studies have shown that women can earn a climax through 5% of their time. In most cases, the birth=factor can be attributed to a decrease in the flow of the genital area, especially in the negative 0. The production of ί方ΐ and medicines, illicit drugs and alcohol abuse can contribute to sexual function: barrier = some different tables The drug or medicinal agent will cause the stagnation of the sexual demand to evoke the disease, and some drugs will cause a high sexually neutral number in the "normal" </ br> barrier or _1 will increase to 68 non-dysfunctional Functional desire, arousal, increase in the six-phase pain of the disk, money and money phase = rate reduction and sexual intercourse _ or sexual intercourse pain 97444 - invention patent specification 3 200927109 Anyway, 'the majority of women still have sexual dissatisfaction' It is not intrinsically true medical dysfunction or accompanied by menopause. The general population of these women hopes to improve their sexual performance by achieving sexual satisfaction or by and/or enhancing orgasm. 5 ❹ 10 15 ❹ 20 Products that are marketed in the market claim to be a lubricious lubricant or intended to stimulate the clitoris to increase the persistence and strength of the orgasm. Most of these components claim to act as a vasodilator to increase sensitivity. ^ For example, 'Products containing final acid include Climatique sold by Climatique International Inc.' Ioxora, New York, USA, 175 New York City I〇x〇ra Biomedical Company, Emerita8, Portland, USA 97205 Portland, USA Emerita Response manufactured by Vibrel® manufactured by GlycoBiosciences of Canberra, Canada. However, these products containing niacin are aqueous compositions and when applied to the skin, cause skin irritation, itching and/or redness, which is called, flushing, and will last for a long time. Therefore, for women and men, it is desirable to achieve or enhance sexual satisfaction or improve sexual ability by means of achieving and/or enhancing sexual distress. Similarly, a qualitative It is also desirable to test the actual blood flow of the human skin area quantitatively and to monitor changes in the blood flow. The methods and compositions of the present invention are responsive to these needs. We have found that the anhydrous composition comprising the vasodilator The blood flow is increased by the object ^ does not cause the skin to be flushed or reddened. (d), the vasodilation of the composition of the present invention can be controlled because the anhydrous matrix acts as nicotinic acid and / 3 /, his effective vasodilator The task of infiltrating into the deep layers of the tissue, the group 4 200927109 :: the human theory theoretically penetrates at least to the stratum corneum and preferably the epidermis. This will increase the number of Ling L's heart and no unwelcome flash red SUMMARY OF THE INVENTION Accordingly, the present invention is directed to an anhydrous composition comprising a vasodilator and an acceptable carrier, wherein the vasodilator is present in an amount effective to increase blood flow when the composition is applied to human tissue. The cover water composition of the present invention preferably contains less than 2% water, more preferably less than about 5% water, and is about 3% water. In another embodiment, the present invention is A method of enhancing an individual's sexual response or sexual well-being, comprising an anhydrous composition comprising an effective amount of a blood-tube dilator, administered to an individual's genital area. In another embodiment, the present invention relates to improvement A method of measuring the efficacy of a sexual blessing, comprising: β &amp; (a) establishing a baseline benefit value to measure blood flow in a personal target zone; (b) after step (a) 'contracting the composition Target area; (c) After step (b) 'measure the blood flow value of the target area; (d) compare the value obtained in step (a) with the value obtained in step (c), where the value and step (in the step (0) a) The difference in the value obtained indicates the increase or decrease in the individual's sexual well-being Insufficient strength. I believe that for those skilled in the art, the following descriptions can be made to make the best use of the present invention. The following specific examples need to be interpreted as only specific instructions, regardless of The invention is not limited in any way, and all technical and scientific terms used herein have the same meaning as those skilled in the art to which the invention pertains, unless otherwise defined. 'Any percentage (%) concentration of the composition is percentage by weight (weight/weight). The present invention relates to a composition which is less capable of being used by both men and women. This sexual ability enhances the composition by Increases blood flow to the sexual regions of men and women. Since the target area of such a composition is local, 10 such a composition does not cause side effects from dysfunctional drugs that affect the systemic erection. For example, there are similar mechanisms in the male and similar drugs used in males and used in other active compositions in FSD (female sexual dysfunction) compositions. Unpleasant side effects, such as topical administration of testosterone service 'or other topical or systemic administration service of hormone containing drug. This unpleasant side effect includes, for example, blood pressure lowering, blood clot formation, heart attack and cancer. The main objects of the sexually enhanced composition of the present invention are as follows: • Vasodilation to increase blood flow in the clitoris and vagina β • Increase sensitivity or provide a feeling of reluctance. 20 • Avoid flushing. These objects can be achieved by the administration of the anhydrous composition of the present invention. The composition comprises, consists essentially of, and consists of a vasodilator and an acceptable carrier. Suitable vasodilators include nicotinic acid derivatives such as nicotinic acid, also known as niacin or vitamin Β3, 6 200927109 nicotinates, for example, nicotinate, nicotine 〇〇tinamide, methyl mC〇nate and niacinamide. It is believed that other vasodilators, in particular, vasodilators that are capable of at least penetrating the stratum corneum and preferably the epidermis to penetrate deep into the tissue without causing flushing 5 will effectively achieve the desired composition and method of the present invention. Capsules of blood can be classified as endogenous (eg, usually manufactured in the body) or exogenous (eg, usually manufactured in vitro). The endogenous dilator is preferably ❹ &amp;-------------------------- Exogenous vasodilators include - nitric oxide inducers and PDE5 inhibitors. - Nitric oxide inducers include glycerol nitrate vinegar (generally known as nitroglycerin) 'isosorbide mononitrate, isosorbide dinitrate, quaternary phosphonium tetranitrate and sodium nitroferric hydride. PDE5 inhibitors include oxime, rhinoceros, leviz, caffeine and papaverine. 15. In a specific embodiment, a preferred vasodilator is one which normally causes a body in an aqueous solution, but does not cause flushing in the composition of the present invention. © Specifically, the constituent material according to the present invention contains a secret acid derivative or contains, for example, less than 0.1% of a nicotinic acid derivative. In a specific example, the preferred derivative of nicotinic acid or niacin is nicotinic acid A 20 = two which has been found to have an unpleasantly strong odor. - In general, the final test ^What organisms exist in the anhydrous composition _ the amount can effectively increase ▲ flow to the human group =. In one embodiment, the vasodilator is present in an amount from about 5% to about 5%, such as from about 0.1% to about 0.2% by weight. Depending on its effectiveness, the composition of the anaesthetic and endogenous vasodilators may be present in a relatively small range. For example, preferably from about 0.05 to about 15 weight gamma, t. The inclusion of an acceptable carrier 骱-term means any object that does not interfere with the purpose of the invention: Ο 10 15

</ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; Examples include polyethylene glycol (abbreviated as fEG). Polyglycol ethers can also be used, including PEG ethers of propylene glycol, glyceryl stearate, propylene glycol oleate and propylene glycol cocoamate, and the like. Specific examples of such PEG assays include PEG-25 propylene glycol stearate, pEG_55 propanol / by k g. Preferably, at least one polyol of the composition of the present invention is a polyalkylene glycol or other group selected from the group consisting of glycerin, propylene glycol, butanediol, hexanediol or polyethylene glycol of different molecular weights and the like and/or Its combination. More preferably, the composition of the present invention contains polyethylene glycol; particularly preferably, the polyethylene glycol may be selected from the group consisting of polyethylene glycol 400 or polyethylene glycol 300. Different molecular weights of polypropylene glycol can also be used. A PEGylated compound such as a peptide or protein derivative obtained by a PEGylation reaction can also be used. Further, block copolymers of PEG such as (ethylene glycol)-block poly(propylene glycol)-block-(polyethylene glycol), poly(ethylene glycol-ran-propylene glycol), and the like can also be used. . The composition of the present invention should contain from about 80% to about 98% by weight of the polyol composition. Preferably, the composition of the present invention contains at least one polyol, more preferably at least two polyols. Preferably, the polyol portion of the composition of the present invention may comprise one or more polyols, such as alkylene glycols and others selected from the group consisting of Dingle 8 20 200927109 Group: different molecular weights of glycerol, propylene glycol, butylene glycol, hexane Alcohol or polyethylene glycol, and the like and/or combinations thereof. More preferably, the composition of the present invention contains a polyvinyl alcohol, and particularly preferably a polyethylene glycol is selected from the group consisting of polyethylene glycol 4 or polyethylene glycol 300. The compositions of the present invention should contain a polyol in an amount from about 80% to about 98% by weight of the composition. In a preferred embodiment, the carrier is a mixture of polyethylene glycol and propylene glycol as described in U.S. Patent No. 7, 5,4,8, the disclosure of which is incorporated herein by reference. . For example, the polyol is a mixture of polyethylene glycol, such as polyethylene glycol 400 and propylene glycol, wherein the weight ratio of polyethylene glycol to propylene glycol is about 3: 1 ° suspension I,, polyethylene glycol in the conversion The degradation is much faster than its aqueous solution. The degradation of the polyethylene glycol causes a odor odorant to prevent the occurrence of odor. Examples of suitable antioxidants include alpha-tocopherol, alpha-probiotic acetate, and butyl

(Li), anti-bad areas, fertility and gallnuts U. For example, US Patent No. 3,592 in the application filed on Apr. 13, 2006, the disclosure of which is hereby incorporated herein by About 3 tongue 曰-+ machine emulsified to about 1.7 wt%. The weight of the group 1 is present, preferably 0.05%. In the example, the composition according to the present invention may include == which provides a user-cue, that is, a US provisional patent application that results in a bloodline such as, for example, a request. The description of the soft material of the slaughter number H illusion 1/842487 and 帛 (10) side is not included in this case as a reference 9 200927109 test. Examples of perceptual transfer agents include decyl salicylate, maleic acid lactate, and methyl acetate. In one embodiment, the compositions of the present invention further comprise at least one sensitizer to enhance sensitivity. In general, the sensitizer can be present in the range of from about 0.05 to about 55 percent by weight. Although its primary role is the increase in sensitivity, it can be divided into two separate types. Such a sensitizer of the first type is a cooling compound, particularly a non-menthol alcohol cooling compound, for example, which is disclosed, for example, in the absence of menthol and is cooler than menthol 'John c. Lefingwell, Ph. D. , Leffingwell &amp; ίο Associates, April 19, 2007. These include WS-23 (2-isopropyl-N, 2, 3) sold by Millennium Chemicals, Inc., 6th Crestwood Street, Jacksonville, FL 32208-4476 - triamyl succinimide), WS-3 (N-ethyl-p-captan-3-carboxyguanamine) and WS-5 [ethyl 3-(p-caprol-3-carboxyguanidino)-B Acid ester]. Among the products, ws_5 is a 15% ice cream for commercial ice, which has recently been licensed by GRAS. It also includes menthone glycerol ketal (sold by Haarmann &amp; Reimer as Frescolat® @ MGA). The spin and left-handed forms appear on the FEMA grAs list but the left form: the form appears to be a commodity. (a) _ lactic acid cover vinegar (sold by Haarmann &amp; Reimer as Frescolat® ML). Also included (-) _ isocean mint 20 Alcohols are sold under the trade name "CoolactP®" by Takasago International Inc. Examples of sensitizers of the second type are temperature-increasing compounds which act to exotherm by exothermic reaction or activation by chemical acceptors. Including the pepper test from pepper or black and white pepper, 1-ethyloxy oxyphenol phenol acetate, from the large 200927109 5 Ο 10 15 ❹ galangiagalang (alpiniagalangal), the stimulating main composition of Shansools, especially Sichuan pepper and ginger extract from α-radio shansool, supplied by Givaudan Fragrances, 1775 Wenshang Road, Kyoc, 07666, USA, with Philadelphia Market Street, Pennsylvania, 19104-3308 No. 500, Timurol from Napalese pepper, supplied by Monell Chemical senses Center. These compounds produce an attractive warming and tingling sensation. Also included in this category are orange peels, and special It is a glucose-based orange peel that is selected by Hayashibara International, Fetcham Park House, Lower Rod, Fetcham, Leathead, Surrey, KT229HD, UK. The third type of sensitizer is a pungent compound that is cooled or warmed. The compounds are different. These compounds cause or cause a pleasant buzz or vibrational sensation. These include the following: Shansools, especially by Jivaudan SA, 5, Chemin de la Parfumerie CH-1214 Vernier, Geneve, A-jingjishansool' from Sichuan Pepper sold by Switzerland and Post Office Box 932 from Roxley City, New Jersey 07747-0923, No. 4, Regal Road, PO Box 932, Takasago International

The spilanthol, which is marketed by the company and derived from the Jumboo extract. These also include the 3500, Philadelphia Market Street, Philadelphia, 19104-3308, sold by Monell Chemical Senses Center, from Timurol, Nepalese Pepper. The compositions of the present invention also include a cellulose-based lubricant and viscosity agent as disclosed in U.S. Patent No. 7,005,408, the disclosure of which is incorporated herein by reference. Examples thereof include carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl 11 20 200927109 methyl cellulose 'especially hydroxypropyl cellulose sold under the trade name KlucelHF by Aqualon, Delaware, USA . Such cellulose-based lubricants and viscosifiers can be incorporated from about 0.05% to about 5% by weight, such as from 0.4% to about 3% by weight. 5 Ο 10 15 〇20 In one embodiment, from about 0.10% to about 0.2% by weight of a vasodilator, such as a nicotinic acid derivative, preferably niacin, from about 0.05% to about h5% by weight, is present in accordance with the present invention. The sensitizer or combination thereof, from about 20% to about 80% polyethylene glycol 400' from about 20% to about 80% propylene glycol, from about 0.2% to about 1.5% propylcellulose and about 〇〇5 To about 1 5% or from about 5% to about 3% of alpha-tocopherol acetate or from about 0.05% to about 3%. The composition of the present invention can be prepared by a conventional technique for preparing an anhydrous composition. See, for example, U.S. Patent No. 7,005,408, the disclosure of which is incorporated herein by reference. For example, acceptable carriers are propylene glycol and/or polyethylene glycol 4, and optionally a lubricant and a viscosity agent, KlucelHF is mixed at about 50 ° C (45 ° C ~ 55 ° 直至 until uniformity is obtained) Gel. Add the vasodilator to the above gel in constant mixing until completely dissolved. Add sensitizer and other optional components if possible. The batch is cooled to room temperature and continuously mixed. If desired, the antioxidants are mixed until such complete dissolution. The compositions of the present invention can be applied to human tissues, such as the genital area of a male or female, skin or mucosa, preferably as disclosed in U.S. Patent No. 7,005,408. Vaginal or oral mucosa, which is incorporated herein by reference. The composition of the present invention may be liquid, semi-solid, 12 200927109 or solid in its intended form. The 18th of the present invention may also be formulated. It becomes a soft or hard gelatin capsule, a suppository, and is impregnated with a textile or a polymer. The composition of the present invention can be made into a tamp Qn coating or dispersed throughout an absorbent tampon material. In the fourth embodiment, the composition of the present invention is administered between about 5 and @30 minutes before sexual intercourse. 10 15 0 The blood flow to the treatment area returns to normal blood flow in a short period of time, for example, within hours, preferably less than 1 hour after sexual intercourse. The composition and method of the present invention surprisingly cause an increase in blood flow However, it does not cause the skin&quot;flushing&quot;. As used herein, "flushing" is a skin reaction to a topical application of the substance, including redness, swelling, swelling, or irritation at the site of application. The total waterlessness provided by the active vasodilators - interaction and vasodilation - results in an effective increase in blood flow to the blood +. The refractory vessel made by the present invention is (mC 〇 tm1C acid). As discussed above, in water-based compositions containing niacin, such as Vibrel manufactured by Glyc〇m〇sciences, Inc., Canberra, Canada, there is extended skin and tissue &quot;flushing and redness. This is = final test in the composition The acid remains in the outer layer of the skin. n , , , ^ In the composition according to the invention, the vasodilation is controlled by the vasodilating weight, for example, the secret acid derivative A 1 used (heart to 0.5%) And because the unique anhydrous matrix serves as the task of infiltration of blood into the deep layers of the tissue, it is inferred that it penetrates at least 1 to the layer and preferably the epidermis. This causes the required blood flow to increase and the flushing effect required for the shell. 20 200927109 In another embodiment, the present invention relates to the use of a laser Doppler image to measure an increase in blood flow and ash flow in the skin. Accordingly, the present invention is also directed to the efficacy of a composition of improved well-being. A method of measurement comprising: (4) establishing a baseline linear welfare value by measuring blood flow in a personal target zone; (b) administering the composition to the target zone after step (a); (c) at step ( After b), measure the blood flow value in the target zone; O (d) compare the value obtained in step (a) with the value obtained in step (C), wherein the difference between the value obtained in step (C) and the value obtained in (iv) (a) Indicates the strength of the individual's 10 plus or minus in sexual well-being.曰 Laser Doppler Image (&quot;LDI") is a technique for monitoring the blood flow of skin towels. LDI analysis uses low-power laser light to penetrate the skin (less than about G.2mm) to read the interaction of the moving material. The light_device is used to measure the frequency of the scattered light. According to the Doppler effect, the moving blood cells will cause the frequency of the backscattered light to change, while the non-moving tissue will scatter the light back at the same frequency. The change in frequency is directly proportional to the number of moving cells (blood flow). Using this principle, LDI is used to scan the skin area and cause a secondary perfusion image of the skin. All women's sexual well-being, or female sex Happiness can also be measured using the FSWB scale meter. There are five main areas of measurable FSWB, including: (1) sexual intercourse between people, (2) emotional sex, and (3) sex. Arouse natural lubrication, (4) sexual orgasm satisfaction, and (5) artificial lubrication. These areas present four main views of female sexual well-being: (丨) physical reactions and feelings' (2) emotional and cognitive Elements, (3) depends on before and after behavior 20092 The factors of 7109 (contextuall) are communicated with (4). We can expect to use the composition and method of the present invention to improve the individual's FSWB score, initially obtaining low scores in the five main areas of FSWB and/or using this book. The compositions and methods of the invention then maintain a high score of FSWB scores in these fields. 5 The LDI test procedure used in the present invention was performed using Molex Instruments, Moer LDI2-IR to measure before and after application of different test samples. Forearm blood flow. Alternatively, the four-dimensional high-resolution laser Doppler imager (HR) produced by the primed ❹ Μ ' Box 564 ' SE-17526 Jarfalla ' in Stockholm, Sweden. A suitable amount, for example, 丨 ml to 3 10 ml of the test sample is applied to the forearm and gently rubbed on the skin for 3 minutes. The composition of the present invention contains a higher potency vasodilator which can be applied in an appropriate amount of from about 0.1 to about 0.5. The liter is more preferably about 2 to about 4 ml and particularly preferably about 0.3 ml. • The sample of the test composition can be applied in the following manner: in the hands of the forearm, between 15 and 15 Wash and dry with a paper towel. Samples of the test compound that were tested after waiting for A for about 1G minutes were filled to a 3 ml level in a 5 ml plastic syringe. The contents of the syringe can now be carefully squeezed throughout - only the middle of the forearm. The index finger and the middle finger of one hand spread the sample evenly over the entire forearm and gently rubbed the entire arm for about 32 〇/min. Now the same procedure is repeated to hold the reference baseline sample in the other Arm.", both arms can now be placed on the platform of the laser light of the LDI device and scanned for 3 minutes. 15 ❹ 10 15 ❹ 200927109 Before and after the smear application and after the application of the sample 3 = Yes; what people need most is after the sexual activity, the blood flow returns to the sample of the composition of the second. This experiment is in contrast to Example 4, (iv), and the blood flow has a gradual decrease to ~:; 5 is a decrease of 36% from the decrease of Example 4 to a decrease of about 5 in the case of 55 minutes. The calculation of 〇0/〇〇 money value is performed using LDI Mohr image analysis (4) and the average blood machine (★ can be in arbitrary units) is calculated at each time point. For example, in Figure 2 and Figure 5, Figure 6, Figure 8 and Figure 1 show a bar graph showing an increase in blood cooling after the formulation is applied, and the LDI image is shown in Figures 3, 7, 9 and 1 . As described above, the composition according to the present invention is non-flushing. Generally speaking, an increase in blood flow greater than 300% will cause flushing. Thus, in one embodiment, the composition according to the present invention may indicate an increase in blood flow of less than 3%, preferably from about 50% to about 150%.乂 The present invention will now be described by way of the following non-limiting examples. [Embodiment] Embodiment 1. Composition! Polyethylene glycol 400 (% by weight/weight) 75.00 20 200927109 Propylene glycol 24.60 Hydroxypropyl cellulose (Klucel HF) 0.30 Dl-indole-tocopherol (vitamin E alcohol) 0.10 Total 100.00 The composition of Example 1 was produced as follows: 1. The following items are added to the manufacturing container: _ Propylene glycol ^ Polyethylene glycol 400

Klucel HF 2. When heated to about 50 ° C (45 ° C ~ 55 ° C), use a Silverson mixer to mix until a uniform gel is obtained. 3. Cool to room temperature 1Ό 4. Add tocopherol and mix until dissolved. Example 2.

(% by weight/weight) 0.10 75.00 24.50 0.30 0.10 100.00 Ingredients in acid (Nicotinic Acid) Polyethylene glycol 400 Propylene glycol hydroxypropyl cellulose (Klucel HF) Dl-Α-tocopherol (vitamin E alcohol) Total 17 200927109 The composition of Example 2 was manufactured as follows: 1. The following were added to the manufacturing vessel: propylene glycol

Polyethylene glycol 400 Klucel HF for acid testing ❹ 10

2. When heated to about 50 ° C (45 t: ~ 55 ° C), mix using a Silverson mixer until a uniform gel is obtained. 3. Cool to room temperature 4. Add alpha-tocopherol and mix until dissolved. Example 3. Composition (% by weight/weight) Nicotinic Acid 0.50 Polyethylene glycol 400 75.00 Propylene glycol 24.10 Hydroxypropyl cellulose (Klucel HF) 0.30

Dl-Α-tocopherol (vitamin E alcohol) 0.10 Total 100.00 The composition of Example 3 was produced as follows: 15 1. The following were added to the manufacturing vessel. Propylene glycol Polyethylene glycol 400 18 200927109

Klucel HF in face acid 2. When heated to about 50 ° C (45 ° C ~ 55. 〇 use a Silverson scrambler to mix until a uniform gel is obtained. 5 3. Cool to room temperature 4. Add α-tocopherol and Mix until dissolved. As shown in Fig. 1, it can be confirmed that the average blood flux is larger than that of Example 2 containing 〇1% nicotinic acid, as in Example 3 containing 〇.5% nicotinic acid. 3 means the rate of ''blood flow through this zone' or 'volume'. The figure shows the amount of parallelism or flow rate before the sample is applied and 3 minutes after the sample is applied. It is further demonstrated that the percentage change of blood flow from baseline is compared with Example 2 containing 0.1% nicotinic acid as an example containing 〇_5% nicotinic acid; 3 is larger. Figure 2 shows the flow rate before and after treatment. The difference between the two is calculated on a % basis. For example, in Example 1 (Figure 3), the amount of treatment before treatment is about 190 and after treatment is about 255. The difference is 65. Divide by 190 by 65. Multiplying this result by 1〇〇, we can get about 34%, which is very close to the third example of the third figure. As shown in Figures 1 and 2, The greater the percentage of nicotinic acid in the composition, the faster the increase in blood flow. Figure 3 shows the laser of the right and left arm skin after application of the composition of Example 2 (left arm) and the right arm of the example). Doppler Image (&quot;LDI"). The left arm image treated with the composition of Example 2 containing 0.1% nicotinic acid showed a lower °/〇 blood flow change of 19 200927109, and contained 5% 5% of the smoke. The right arm image of the composition treated with the alkaline acid of Example 3 showed a higher % blood flow change in comparison. The red color indicates the highest blood flow and the blue color indicates the lower % blood flow change region. (% by weight / weight) 0.3 0.20 75.00 24.10 0.30 0.10 100.00 Ingredients Nicotinic Acid Polyamido Glycol 400 Propylene Glycol Hydroxypropyl Cellulose (Klucel HF) D1-A-Tocopherol (Vitamin E Alcohol) The composition of the above Example 4 was prepared in the following manner: ❹ 10 1. The following were added to the propylene glycol in the manufacturing vessel.

Polyethylene glycol 400 Klucel HF 2. When heated to about 50C (45 ° C ~ 55. 混合 use a silvers 〇n stirrer until a uniform gel is obtained 3. The following system is used to mix the mixture of tai plus step 2 Until completely dissolved: Nicotinic acid 20 15 200927109 Nicotinamide 4. Cool the mixture to room temperature 5. Add α-fertility (vitamin £) and mix until dissolved.

10 Figure 10 shows that for the safety of smear, blood flow decreases over time. Figure 10 is a blood flow from the baseline monitored by LDI when the subject's left forearm and right forearm were rubbed in 3 ml for 3 minutes in the same coffee test. Change the bar chart. The LDI test was performed for 60 minutes and the rate of change in blood flow was recorded after 3 minutes (immediately after treatment), after 15 minutes, after 35 minutes, and after 55 minutes. Fig. 11 is a photograph of the LDI of Fig. 10 showing a progressive decrease in the % blood flow of both Example 1 and Example 4. Example 5. fe component amount/weight) Nicotinic Acid Ginger extract polyethylene glycol 400 propylene glycol hydroxypropyl cellulose (Klucel HF) Dl-indole-tocopherol (vitamin E alcohol) Total 0.10 0.10 75.00 24.40 0.30 0.10 100.00 The above composition of Example 5 was prepared in the following manner: 21 200927109 1. The following were added to the manufacturing vessel: propylene glycol

Polyethylene glycol 400 Klucel HF 5 ο 10

2. When heated to about 50 ° C (45 ° C ~ 55 ° C) using a Silverson mixer until a uniform gel is obtained 3. The following are added in a mixed manner to the mixture of step 2 until completely dissolved: Test the ginger extract 4. Cool the mixture to room temperature 5. Add alpha-tocopherol (vitamin E alcohol) and mix until dissolved. Example 6. Composition (% by weight/weight) Nicotinic Acid 0.10 α-Glucosyl Orange Peel 0.10 Polyethylene glycol 400 75.00 Propylene glycol 24.40 Hydroxypropyl cellulose (Klucel HF) 0.30

Dl-indole-tocopherol (vitamin E alcohol) 0.10 total 100.00 The composition of Example 6 was prepared in the following manner: 22 15 200927109 1. The following were added to the manufacturing vessel propylene glycol

Polyethylene glycol 400 Klucel HF 5 2. When heated to about 50 ° C (45 ° C ~ 55 ° C) using a Silverson mixer until a uniform gel is obtained 3. The following are added in a mixed manner in step 2 The mixture is completely dissolved until it is completely dissolved: ίο α-glucosyl orange peel 4. The mixture is cooled to room temperature 5. Add α-tocopherol (vitamin sterol) and mix until dissolved. Example 7. Composition (% by weight/weight) of acid (Nicotinic Acid) ginger extract polyethylene glycol 400 propylene glycol hydroxypropyl cellulose (Klucel HF) Dl-Α-tocopherol (vitamin E alcohol) total. 50 0.10 75.00 24.00 0.30 0.10 100.00 The composition of Example 7 was prepared in the following manner: 23 200927109 1. The following were added to the manufacturing vessel: Propylene glycol

Polyethylene glycol 400 Klucel HF 5 Ο 10

2. When heated to about 50 ° C (45 ° C ~ 55 ° C) using a Silverson mixer until a uniform gel is obtained 3. The following are added in a mixed manner to the mixture of step 2 until completely dissolved: Test the ginger extract 4. Cool the mixture to room temperature 5. Add alpha-tocopherol (vitamin E alcohol) and mix until completely dissolved. Example 8. Composition (% by weight/weight) Nicotinic Acid 0.50 α-Glucosyl Orange Peel 0.10 Polyethylene glycol 400 75.00 Propylene glycol 24.00 Hydroxypropyl cellulose (Klucel HF) 0.30

Dl-indole-tocopherol (vitamin E alcohol) 0.10 total 100.00 The composition of the above Example 8 was prepared in the following manner: 24 15 200927109 1. The following were added to the manufacturing container: propylene glycol

Polyethylene glycol 400 Klucel HF 5 ❹ 10

2. When heated to about 50 ° C (45 ° C ~ 55 ° C), use a Silversho mixer to mix until a uniform gel is obtained. 3. The following are added to the mixture of step 2 in a mixed manner until completely dissolved: In the acid test α-glucosyl orange peel 4. Cool the mixture to room temperature 5. Add α-tocopherol (vitamin sterol) and mix until dissolved. Example 9. Group composition (% weight / weight) Acid methyl hydrazine 0.20 in acid test 0.20 polyethylene glycol 400 75.00 propylene glycol 24.20 hydroxypropyl cellulose (Klucel HF) 0.30 Dl-indole-tocopherol (vitamin E alcohol) 0.10 total 100.00 composition of the above example 9 The system was prepared in the following manner: 25 15 200927109 1. The following were added to the manufacturing vessel: Propylene glycol

Polyethylene glycol 400 Klucel HF 5 Ο 10 2. When heated to about 50 ° C (45 ° C ~ 55 ° C) using a Silverson mixer until a uniform gel is obtained 3. The following are added in a mixed manner Mixture of Step 2 until completely dissolved: Salicylic acid formazan is intended for acid testing. 4. Cool the mixture to room temperature. 5. Add alpha-tocopherol (vitamin E alcohol) and mix until dissolved. Example 10. Group composition (% by weight/weight) Salicylic acid formazan 0.20 Lactic acid capping 0.20 Polyethylene glycol 400 75.00 Propylene glycol 24.20 Hydroxypropyl cellulose (Klucel HF) 0.30 Dl-indole-tocopherol (vitamin E Alcohol) 0.10 Total 100.00 The composition of the above Example 10 was prepared in the following manner: 26 200927109 1. The following were added to the manufacturing vessel: propylene glycol

Polyethylene glycol 400 Klucel HF 5 ❹ 10 2. When heated to about 50. (:(45.(^55.〇) Use 8丨^^〇11 stirrer to mix until a uniform gel is obtained. 3. The following items are added to the mixture of step 2 in the mixture until the solution is completely dissolved. Methyl ester lactate lactate 4. Cool the mixture to room temperature 5. Add alpha-tocopherol (vitamin E alcohol) and mix until dissolved. Example 11. (Kappa-Υ warming liquid with 0.2% nicotinic acid) Prescription) The composition of the above Example 11 was prepared in the following manner: 1· The following were added to the manufacturing container: Group composition KY warm liquid®!; by New Jersey 99, USA 99558-9418 Skillman City McNeil-PPC The company's personal products company sales) Nicotinic acid λ. 27 200927109 2. When heated to about 50 C (45 ° C ~ 55 ° C), use Silverson to mix the crying, early morning until the average - (four) ° 3. Cooling to room temperature 5 Example 12. (Romanta Therapy® sold by Passion, Las Vegas, Nevada 89119-4436) ❿ ΜΛβ: Weight/weight) (unknown) Whole leaf aloe concentrate pure water

Sorbitol USP Hydroxyethyl Cellulose Saw Palmetto Extract 'Soybean Protein

Mint USP Complex 5 (with a patented blend of five essential components)

L-arginine, USP Steviopurinyl light benzoic acid US USP Example 13. G, 0.2 A in acid-reactive κ_γ Warming Ultragel® formulation) The composition of the above Example 13 was prepared in the following manner: 1 Add the following to make the container: 28 200927109 Composition (% by weight/weight) KY Warming Ultragel (sold by the Personal Products Division of McNeil-PPC, Skillman City, USA 9858-9418 Skills City) Nicotinic Acid 0.2 2 When heated to about 50 ° C (45 ° C ~ 55 ° C), use a Silverson dispenser to mix until a uniform gel is obtained. 3. Cooling to room temperature Example 14 (KY Liquid® formulation with 0.2% nicotinic acid) The composition of Example 14 above was prepared in the following manner: 1. The following were added to the manufacturing vessel: /weight) KY Liquid (by Skills City, 99.8 08558-9418, New Jersey, USA)

McNeil-PPC's Personal Products Division is responsible for the sale of acid (X2 2. When heated to about 5 (TC (45 ° C ~ 55. 〇 use a Silverson mixer to mix until a uniform liquid is obtained 3. Cool down to room temperature 29 200927109 Example 15 (Excite ®, sold by J〇rdyn Nicole) %Weight/Weight Unknown demineralized water Sodium benzoate Sodium sorbate Sodium arginine lysine Epimedium extract Mercapto hydroxybenzoic acid Ester glycerol

Yamanium-alcohol via ketone-based cellulose vitamin E as shown in Figure 4, which is a plot of 2 ml of the composition of Examples 11-15 after being manually rubbed onto the subject's forearm and monitored by LDI A bar graph of changes in blood flow at baseline. Figure 4 demonstrates the following: (4) Anhydrous Example 13 KY Warming Ultragel with 0.2% nicotinic acid is superior to aqueous Example 14 (κγ liquid 〇. 2% nicotinic acid). It is also superior to Example 12 (R〇manta8 treatment) and Example 15 (Excite®); 30 200927109 (b) Anhydrous Example 13' (KY Warming Ultragel with 0.2% nicotinic acid) is also superior to anhydrous Example ll (KY warming liquid with 0.2% nicotinic acid; and (c) anhydrous Example 13 is superior to Example 11 because it is compared with 5 25% polyethylene glycol 400 of Example 11 75% polyethylene glycol. (% 詈 / ϋ! 25.00 75.00 !〇0.00 Example 16. (Waterless placebo) Group ingredients Glycerol propylene glycol The composition of the above Example 16 is manufactured in the following manner: ίο

1. The following items are added to the manufacturing container: Glycerin Propylene Glycol 2. When heated to about 50. (: (45. 〇 - 55 ° 〇 Mix with 811 〃 milk 011 stirrer until a homogeneous solution is obtained. 15 Example 17. (Anhydrous with 0.2% nicotinic acid and 0.3% niacin) Sister ingredients (% by weight /重詈) Glycerin 25.00 Propylene glycol 74.50 Nicotinic acid 0.20 31 200927109 Nicotinamide 0.30 Total 100.00 The composition of the above composition 17 is produced as follows: 1. The following materials are added to the manufacturing container: Glycerol propylene glycol is tested for acidity

10

Nicotinamide 2. When heated to about 50 ° C (45 ° C ~ 55 ° C), mix using a Silverson mixer until a uniform gel is obtained. 3. Cooling to room temperature Example 18 (aqueous placebo) Composition (% by weight/weight) Propylene glycol 35.00 Pure water 65.00 Total 100.00 The composition of the above composition 18 was produced as follows: 15 1. The following were Add to manufacturing vessel: Propylene glycol water 32 200927109 2, when heated to about 50 ° C (45 ° C ~ 55. 〇 use a Silverson mixer to mix until a homogeneous solution is obtained. Example 19. Group composition (containing 0.2% nicotinic acid and 0.3% aqueous composition of nicotinamide) (% by weight/weight) 丙 Propylene glycol in acid nicotinamide 35.00 0.20 0.30 pure water 64.50 Total 100.00 The composition of the above Example 19 was produced as follows: 1. The following The material was added to the manufacturing vessel: Propylene glycol nicotinic acid 10 Nicotinamide 0 Water 2. When heated to about 50 ° C (45 ° C ~ 55 ° C), use a Silverson mixer to mix until a homogeneous solution was obtained. (Aqueous composition containing 2% arginine) Group composition (% by weight/weight) 35.00 2.00 Propylene glycol arginine 33 200927109 Pure water 63.00 Total 100.00 The composition of the above Example 20 was produced as follows: 1. Things are added In the manufacturing container: propylene glycol 5 Ο arginine pure water 2. When heated to about 5 ° C (45 ° C ~ 55 ° C) using a Silverson mixer until mixing to obtain a uniform solution. Figure 5 for the examples At various times, in a separate experiment, 3 ml of the composition of Examples 16-20 was manually rubbed onto the subject's forearm for 3 minutes and then monitored by LDI from the baseline blood flow line graph. Figure 5 is An example of a water-free aqueous composition is shown. Figure 5 illustrates the following: (a) Example corresponding to the aqueous composition of Example 19 (containing hydrazine, 2% nicotinic acid and 0.3% nicotinamide) and corresponding examples An aqueous placebo of 18 compared to the aqueous composition of Example 2 containing 2.0% arginine, anhydrous Example 17 (containing 2% nicotinic acid and 0.3% nicotinamide) and the anhydrous placebo of Example 16 Increased % blood flow is preferred. (b) Higher % blood flow change in Example 16 (placebo of the anhydrous composition of Example π), which is due to the duration of the higher smear than the implementation of 34 200927109 17 is 咼 because it is applied 3 minutes earlier than Example 17, so the skin on the forearm is better than Example 17 More than 3 minutes. Some patients describe the use of L-arginine in the composition to enhance sexual response, because L-arginine is involved in the physiological pathway leading to vasodilation, and ultimately because L-arginine is Nitric oxide donors cause congestion in sexual organs. However, L-arginine is a vasodilator in tissues and the presence of nitric oxide synthase in tissues is 'no reported evidence of production in human male or female sexual organs or tissues. Nitric oxide enzymes are necessarily associated with sexual arousal and/or orgasm processes. Surprisingly, the present inventors have found that L-arginine (as shown in Fig. 5) containing an aqueous composition and L-arginine containing a commercial Excite® (as shown in Fig. 4), according to Ray The Doppler imaging test did not cause substantial vasodilation. Example 21. Group composition Polyethylene glycol 400 Propylene glycol hydroxypropyl cellulose (Klucel HF) D1-A-Probiotics (Vitamin E alcohol) Total £% ϋ/ϋΐ 75.00 24.40 0.50 0.10 100.00 The composition of the above Example 21 Prepared in the following manner: 1. The following items were added to the manufacturing container: 35 200927109

Propylene glycol polyethylene glycol 400 Klucel HF 2. When heated to 50 ° C (45 ~ 55 ° C), mix in a Silverson mixer until a uniform gel is obtained 3. Cool the mixture to room temperature 4. Add α-fertility Phenol (vitamin E alcohol) and mixed until dissolved.

Example 22. Ingredients (% by weight/weight) Acid test 0.10 Peppermint essential oil (optamint) 0.10 Polyethylene glycol 400 75.00 Propylene glycol 24.20 Hydroxypropyl cellulose (Klucel HF) 0.50 Dl-Α-tocopherol (vitamin E Alcohol) 0.10 total 100.00

G 10 The composition of the above Example 22 was prepared in the following manner: 1. The following were added to the manufacturing vessel: propylene glycol

Polyethylene glycol 400 Klucel HF 36 15 200927109 2. When heated to about 50 ° C (45 ° C ~ 55 ° C), use a Silverson mixer to mix until a uniform gel is obtained. 3. The following are added in a mixed manner. Mix the mixture of step 2 until completely dissolved: 5 in the ozonic acid of alkali acid 4. Cool the mixture to room temperature 5. Add α-tocopherol (vitamin E alcohol) and mix until dissolved. 〇10 Example 23. Component weight/weight) Acidity test 0.30 ohms thin essential oil 0.10 * Polyethylene glycol 400 75.00 Propylene glycol 24.00 Hydroxypropyl cellulose (Klucel HF) 0.50 ◎ Dl-Α-tocopherol (vitamin E Alcohol) 0.10 Total 100.00 The composition of the above Example 23 was prepared in the following manner: 1. The following were added to the manufacturing vessel: Propylene glycol 15 Polyethylene glycol 400

Klucel HF 37 200927109 2. When heated to about 50 ° C (45 ° C ~ 55 ° C) using a Silverson mixer until a uniform gel is obtained 3. The following are added to the mixture of step 2 in a mixed manner until Completely dissolved until acidified peppermint essential oil 8 4. Cool the mixture to room temperature 5. Add α-tocopherol (vitamin E alcohol) and mix until dissolved. 〇 10

Example 24. Group composition (% by weight/weight) in acid test 0.30 ohms thin essential oil 0.20 polyethylene glycol 400 75.00 propylene glycol 23.90 hydroxypropyl cellulose (Klucel HF) 0.50 Dl-indole-tocopherol (vitamin E alcohol) 0.10 Total 100.00 The composition of the above Example 24 was prepared in the following manner: 1. The following were added to the manufacturing vessel: Propylene glycol 15 Polyethylene glycol 400

Klucel HF 38 200927109 2. When heated to about 50 ° C (45 ° C ~ 55 ° C) using a Silverson mixer until a uniform gel is obtained 3. The following are added to the mixture of step 2 in a mixed manner until Completely dissolved until the acid is tested. 4. Cool the mixture to room temperature. _ 5. Add α-tocopherol (vitamin E alcohol) and mix until dissolved. 〇10 Example 25. Component Weight/Weight) Ginseng Occupant Essential Oil Polyethylene Glycol 400 Propylene Glycol via Propyl Cellulose (Klucel HF) Dl-Α-Tocopherol (Vitamin E Alcohol) Total 0.10 0.10 75.00 24.20 0.50 0.10 100.00 The composition of the above Example 25 was prepared in the following manner: 1. The following contents were added in a manufacturing container: propylene glycol 15 polyethylene glycol 400

Klucel HF 39 200927109 2. When heated to about 50 ° C (45 ° C ~ 55 ° C) using a Silverson mixer until a uniform gel is obtained 3. The following are added to the mixture of step 2 in a mixed manner until Completely dissolved until 5 ginseng Ou Tao He essential oil 4. Cool the mixture to room temperature _ 5. Add α-tocopherol (vitamin E alcohol) and mix until dissolved. 〇10 Example 26. Component (% by weight/weight) in the acid test section 0.10 Ou Tao He Essential Oil 0.10 - Polyethylene glycol 400 75.00 Propylene glycol 24.20 ❹ Hydroxypropyl cellulose (Klucel HF) 0.50 Dl-Α- Tocopherol (Vitamin E alcohol) 0.10. Total 100.00 The composition of the above Example 26 was prepared in the following manner: 1. The following were added to the manufacturing vessel: Propylene glycol 15 Polyethylene glycol 400

Klucel HF 200927109 2. When heated to about 50 ° C (45 ° C ~ 55 ° C) using a Silverson mixer until a uniform gel is obtained 3. The following are added to the mixture of step 2 in a mixed manner until complete Solubilize 5 After the acid test, the product is cooled to room temperature. 5. Add α-tocopherol (vitamin E alcohol) and mix until dissolved. 10 Example 27. Component Weight/Weight) Yohimbine 0.10 Oxahe Essential Oil 0.10 * Polyethylene Glycol 400 75.00 Propylene Glycol 24.20 Hydrazine Hydroxypropyl Cellulose (Klucel HF) 0.50 Dl-Α-Tocopherol (Vitamin E Alcohol) 0.10 Total 100.00 The composition of the above Example 27 was prepared in the following manner: 1. The following were added to the manufacturing vessel: Propylene glycol 15 Polyethylene glycol 400

Klucel HF 41 200927109 2·When heated to about 5 (TC (45〇C~55.) Mix using a Silverson mixer until a uniform gel is obtained. 3. The following are added in a mixed manner to the mixture in step 2 until complete Soluble yohimbine base peppermint essential oil 4. Cool the mixture to room temperature 5. Add a-tocopherol (vitamin e alcohol) and mix until dissolved. Example 28. (Vibrel8) (Vibrel 'Canberra, Canada GiyC〇Bi〇sciences company) group of pure water in acid-tested polyvinyl alcohol ethoxylated polyethylene glycol Glyceron propylene glycol carboxymethyl cellulose hydroxyethyl cellulose Figure 6 comparison of the following examples: Example 21 (Anhydrous composition placebo of Example 22) and Example 28 (Vibrel®: manufactured by www.Vibrel.com). Figure 6 is a comparison with Example 21 (Example 22 anhydrous composition of comfort 200927109) The &quot;flushing&quot; product represented by Vibrel (Example 28) is exemplified. Compared with 90% of Example 21, the blood flow of Vibrel changes almost 350 〇/〇. This very south blood flow change becomes the cause of flushing. Moreover, as illustrated in Figure 2, Examples 2 and 3 each contained 0.1 and 0 5% nicotinic acid, which did not cause an excessive blood flow change and both were sufficiently lower than 350%. Furthermore, Figure 7 is Example 21 (left) LDI image of the right arm and left arm skin after 3 minutes of application of the arm of Example 28 (right arm). • The right arm of Example 28 (VIBREL 8) indicates an enlarged area showing excessive blood flow changes. The flow change indicates "flushing", shown in blue. This represents a change in the surface skin of 0. In contrast, the deep layer of the right arm is shown in red. The red and blue areas of the surface blood flow expansion of Example 28 represent ,, flushing, as indicated, the total area covered is even larger. Example 29. (Zestra8) 5 sold by the Women's Consumer Products Division of QualiLife Pharmaceuticals, Inc., Charles City, South Carolina, USA. μ ' 》 Ingredients Free Glass Even Borage Seed Oil Evening Primrose Oil

Angelica extract, mint (Coleus) extract, vitamin C, vitamin E 43 200927109 Figure 8 Comparative Example 3 (anhydrous composition 〇 5% nicotinic acid) and Example 29 (ZESTRA) ' are indicated by bar graphs. ZESTRA does not contain any nicotinic acid and therefore has a lower blood flow change as shown in Figure 8, and Figure 9 is an LDI photograph of Figure 8, which shows the larger red 5 color covered by Example 3. The higher percentage increase in the flow indicated by the blue area, compared to Example 29 (Zestra), as indicated by the smaller red and blue coverage areas, shows a lower % increase in blood flow. Example 30A. (endogenous vasodilator _ tachykinin _ aqueous base) 〇 component pure water soothing kinin total (° / 〇 weight / weight) 99.90 0.10 100.00 The composition of the above Example 30A is as follows Mode Preparation: 1· The following were added to the manufacturing vessel: pure water, USP bradykinin 2. Mixing using a Silverson mixer until a homogeneous solution was obtained Example 30B (endogenous vasodilator _ tachykinin _ non-aqueous base Substance) (% by weight / Cao $ PEG 400 75 〇〇 propylene glycol 24 ^ 44 200927109 0.30 0.10 0.10 100.00 propyl cellulose (Klucel HF) D1_A-tocopherol (vitamin E alcohol) soothing kinin total The composition of Example 30B was prepared in the following manner: L The following were added to the manufacturing vessel: Propylene glycol

Polyethylene glycol 4〇〇 Klucel HF 2. When heated to about 50. (: (45. 〇 55° 混合 mix using a Silverson mixer until a uniform condensate is obtained 3. The following is added in a mixed manner to the mixture of step 2' until completely dissolved: Soothing kinin 4. Cooling to room temperature 5. Add α-tocopherol (vitamin e alcohol) and mix until dissolved. Example 31 (. (exogenous vasodilator / nitric oxide inducer - isosorbide dinitrate - aqueous base) Γ% Cao amount / Weight) 99.90 0.10 100.00 Ingredients Pure water diisosorbide dinitrate total 45 200927109 The composition of the above Example 31A was prepared in the following manner: 1. The following were added to the manufacturing vessel:

Pure water, USP isosorbide dinitrate 2. Mix using a Silverson mixer until a homogeneous solution is obtained.

Example 31B. (Intrinsic vasodilator - isosorbide dinitrate - non-aqueous base) Group composition (% by weight / weight) Polyethylene glycol 400 75.00 Propylene glycol 24.60 Hydroxypropyl cellulose (Klucel HF) 0.30

Dl-Α-tocopherol (vitamin E alcohol) 0.10 isosorbide dinitrate 0.10 total 100.00

The composition of the above Example 31B was prepared in the following manner: 1. The following were added to the manufacturing vessel: propylene glycol

Polyethylene glycol 400 Klucel HF 2. When heated to about 50 ° C (45 ° C ~ 55 ° C) using a Silverson mixer until a uniform gel is obtained 46 15 200927109 3. The following are added in a mixed manner Mixture of Step 2 until completely dissolved: Isosorbide dinitrate 4. Cool to room temperature 5 5. Add alpha-tocopherol (vitamin E alcohol) and mix until dissolved.

Example 32 (Exogenous vasodilator / PDE5 inhibitor - sildenafil citrate • Aqueous base) Group composition (% by weight / weight) Pure water 99.90 0.10 100.00 Total sildenafil citrate 10 Composition of the above Example 32 It is prepared in the following manner: 1. The following items are added to the manufacturing container:

Pure water, USP 昔 sildenafil citrate 2. Mix using a Silverson blender until a homogeneous solution is obtained. 15 Example 32B. (endogenous vasodilator - sildenafil citrate - non-aqueous base) Group composition (% by weight / weight) 75.00 24.60 polyethylene glycol 400 propylene glycol 47 200927109 0.30 0.10 0.10 100.00 propyl cellulose (Klucel HF) D1-A-tocopherol (vitamin e alcohol) sildenafil citrate total The composition of the above Example 32B was prepared in the following manner: 1. The following were added to the manufacturing vessel: propylene glycol

Polyethylene glycol 400 Klucel HF 2. When heated to about 50 ° C (45 ° C ~ 55 ° C), use a Silverson mixer to mix until a uniform gel is obtained. 3. The following systems are added in a mixed manner in step 2 Mixture until completely dissolved: Soothing kinin 4. Cool to room temperature 5. Add alpha-tocopherol (vitamin E alcohol) and mix until dissolved. Example 33. The blood flow changes of the compositions of Examples 30, 303, 31, 3, 32, and 32:6 were used. The compositions of Examples 30, 30, 31, 31, 32 and 32 were applied to the subject's forearm in an amount of one milliliter per application. Blood flow was measured using the LDI technique prior to application, 30 minutes after application and 30 minutes after application of the composition of Example 48 20 200927109 5 Ο 10 15 Ο 20 . No redness, irritation, or itchy skin (such as &quot;flushing" caused by any sample composition was observed, even in the cases of Examples 30, 31, and 32, where increased blood flow was observed. Blood flow rate The difference is calculated on a per-percentage basis for each sample composition. The difference after 5 minutes is illustrated in the graph of Figure 12. The difference after 30 minutes is illustrated in the graph of Figure 13. Example 34. Example Comparison of blood flow between 30 Β, 31 Β '32 Β and Example 22. The compositions of Examples 22, 30 Β, 31 Β and 32 涂 were applied to the subject's forearm arm in an amount of 0.3 ml per application. Techniques were used to measure blood flow, 5 minutes after application and 30 minutes after application of the composition of the examples. No redness, irritation, itchy skin (eg "flushing") caused by any sample composition was observed, or even In the case of Examples 3A, BB and 32b, increased blood flow was observed. The difference in blood flow rate was calculated on a percentage basis to compare the sample compositions of Examples 30B, 31B and 32B with an increase in percentage over Example 22. The difference between 5 minutes and 3 minutes is illustrated in the diagram of the brother 14 chart. While the invention has been described with reference to the specific embodiments, it should be understood that Therefore, the reduction of the number of people in the silk tree can be used as a modification of the number 49 200927109 and the other formulas are defined in the patent application scope as described in the accompanying patent application, in the absence of (four) I invention eve ^ '精神 _ ^ 43 can be carried out under the spirit and scope. [Simple description of the diagram] 5 Ο 10 15 ❹ 20 For a more specific description of this month, the above concise summary can refer to the specific example illustrated in the accompanying drawings. In any case, it should be noted that the drawings merely illustrate the shaft of the present invention and should not be restricted by the material, as the invention may allow other examples of other equivalents to be effective. The Doppler image (&quot;LDI") monitors the skin of the subject's arm, immediately after re-wiping the compositions of Examples 2 and 3, and LDI 3 minutes after application. 3 ml of each composition was manually rubbed on a bar graph of the gold flux of the subject, such as the arm. Figure 2 is a bar graph depicting the rate of change in blood flow from the baseline monitored by LDI after 3 minutes of application. Each of the compositions of Example 2 (left arm) and Example 3 (right arm)) was manually rubbed onto the subject's forearm for 3 minutes. Fig. 3 is an LDI image of the right arm and left arm skin after application of the composition of Example 2 (left arm) and Example 3 (right arm) for 3 minutes. Red shows the highest blood flow and blue shows a lower rate of blood flow change. Figure 3 is a photograph of the picture in Figure 2. Figure 4 is a graph showing the blood from the baseline monitored by LDI after 2 ml of the composition of Examples 11-15 was manually rubbed on the forearm of the subject for 3 minutes at different times for the respective experiments. A bar graph of flow changes. 50 200927109 Figure 5 is a comparison of the examples in different experiments at different times, 3 ml of the composition of Examples 16-20 was manually rubbed on the subject's forearm after 3 minutes. A bar graph of changes in blood flow. When the LDI test of Examples 19 and 20 was carried out, the compositions of Examples 19 and 20 were compared with placebo (Example 丄 8), respectively. Figure 6 is a comparison of the changes in the flow from the baseline monitored by LDI when 3 ml of each of Examples 21 and 28 were manually rubbed on the subject's left forearm and right forearm for 3 minutes in the same LDI test. line graph. Fig. 7 is an LDI image of the skin of the right arm and the left arm after application of the composition of Example 21 (left arm) and Example 28 (right arm) as shown in Fig. 6. Figure 8 is a comparison line of baseline blood flow changes monitored by LDI in the same LDI test when 3 ml of each of Examples 3 and 29 were manually rubbed on the subject's left forearm and right forearm for 3 minutes. Figure,. Figure 9 is an LDI image of Figure 8, which shows a higher ash flow % increase as indicated by the larger red and blue regions covered by Example 3, compared to Example 29 (Zestra) display. The lower blood flow % indicated by the smaller red and blue coverage areas increases. Figure 10 is the same as the LDI test, manually 3 ml of each of Example 4 and Example 1 were rubbed on the subject's left forearm and right forearm for 3 minutes, monitored by LDI from baseline. A comparison bar chart of blood flow changes. The LDI test for the LDI test for 60 minutes and the rate of change of blood flow was recorded at 3 minutes (immediately after treatment), after 15 minutes, after 35 minutes and after 55 minutes. 51 200927109 Fig. 11 is an LDI image of Fig. 10 showing a progressive decrease in blood flow rate of both Example 1 and Example 4. Figures 12 and 13 are in the respective tests for pairing each of Examples a and B, using 0.3 ml of each of Examples 30A, 30B, 31A, 31B, 32A and 32B 5 to manually rub the subject's left arm. A comparison bar graph of changes in blood flow from the baseline monitored by LDI with the right arm over 30 seconds. The blood flow rate of change in LDI data in Figures 12 and 13 was recorded at 5 minutes and 30 minutes after treatment, respectively. Formulation A is applied to the left arm and Formulation B is applied to the right arm of the subject. 10 Figure 14 is used in individual experiments using 0.3 ml of each of Example 22, Example 30B, Example 31B and Example 32B to manually rub the subject's right forearm for 30 seconds, and the blood flow monitored by LDI The comparison of the changes in the line 'Figure. The rate of change in blood flow of LDI data was recorded at 5 and 30 minutes after treatment. Fig. 14 specifically illustrates the rate of change in blood flow in Examples 30B, 31B 15 and 32B as compared with Example 22. ❹. [Main component symbol description] None. 52

Claims (1)

200927109 VII. Scope of Application: 1. An anhydrous composition comprising a vasodilator and an acceptable carrier, wherein the vasodilator is capable of increasing blood flow to human tissue when the composition is used in the human tissue The effective amount exists. 5 10 15 2. The composition of claim 1, wherein the vasodilator is capable of penetrating deep into the tissue without causing flushing of the tissue. 3. The composition of claim 1, wherein the vasodilator is present at from about 0.1 to about 0.5% by weight. 4. The composition of claim 1 wherein the composition is free of acid-reducing derivatives. 5. The composition of claim 1, wherein the carrier is a polyol. 6. The composition of claim 5, wherein the polyol is selected from the group consisting of polyethylene glycol, polyethylene glycol ether, propylene glycol, hexanediol, butylene glycol, and mixtures thereof. 7. The composition of claim 1, wherein the human tissue is a male or female genital area. 8. The composition of claim 6, wherein the polyol is a mixture of polyethylene glycol and propylene glycol. 20 9. The composition of claim 8 wherein the weight ratio of the polyethylene glycol to the propylene glycol is about 3:1. 10. The composition of claim 1, further comprising an antioxidant, the effective amount of which prevents degradation of the polyol. The composition of claim 10, wherein the antioxidant is selected from the group consisting of tocopherol, ascorbic acid, and butylated hydroxyindole (BHT), wherein the polyol is selected from the group consisting of propylene glycol. a group of polyethylene glycol, polyethylene glycol ether, butyl glycol, hexanediol, and combinations thereof. 5. The composition of claim 10, wherein the antioxidant is present in an amount of from about 0.05% to about 3%. 13. The composition of claim 12, wherein the antioxidant D is selected from the group consisting of alpha-tocopherol, alpha-tocopherol acetate, and mixtures thereof. 14. The composition of claim 1, further comprising an effective amount of at least one sensitizer. 15. The composition of claim 14 wherein the sensitizer is present in an amount ranging from about 0.05 to about 5 percent by weight. 16. The composition of claim 15 wherein the sensitizer is selected from the group consisting of a cooling compound, a warming compound, a pungent compound, and a mixture thereof. 15 17. The composition of claim 16, wherein the cooling compound is selected from the group consisting of 2-isopropyl-indole, 2,3-trimethylbutanamine, hydrazine-ethyl-p-carboxylate- 3-Methylamine and ethyl 3-(p-caprol-3-ylamino)acetate menthol glycerol ketal, (-)-lactic acid vinegar, (-)-isomethampin, α- Glucosyl orange peel and its mixture. 2〇18. The composition of claim 15 wherein the warming compound is selected from the group consisting of pepper test, 1-acetoxy pepper, acetic acid S, α-radio shansool, Timurol, orange peel, Ginger extract and mixtures thereof. 54 200927109 19. The composition of claim 14, wherein the pungent compound is selected from the group consisting of Shansools' Spiianth〇i, Timurol and mixtures thereof. 2. The composition of claim 1 further comprising an effective amount of a lubricant and a viscosity agent. 21. The composition of claim 20, wherein the lubricant is selected from the group consisting of strontium methyl cellulose, hydroxyethyl cellulose, hydroxypropyl fluorenyl cellulose, hydroxypropyl cellulose, and mixtures thereof. In groups. 22. The composition of claim 21, wherein the lubricant is present in an amount of from about 5 to about 5% by weight. 23. The composition of claim 3, wherein the composition is non-tidal and the increase in the j&amp;L flow is less than 300%. 24. The composition of claim 1, wherein the composition is capable of infiltrating the epidermis of the human tissue when applied to the human tissue. 25. A method of achieving an increase in a person's sexual well-being characterized by comprising an anhydrous composition that is administered to the individual genital area, the anhydrous composition comprising an effective amount of a vasodilator and an acceptable carrier. 26. The method of claim 25, wherein the composition is administered between 5 minutes and 30 minutes prior to sexual intercourse. 27. The method of claim 25, wherein the vasodilator is present in an amount from about 0.1 to about 5% by weight. 28. The method of claim 25, wherein the conjugate is capable of participating in the epidermis of the human tissue when applied to the human tissue. 29. The method of claim 25, wherein the seed is a polyol. The method of claim 29, wherein the polyol is selected from the group consisting of polyethylene glycol, propylene glycol, polyethylene glycol ether, hexanediol, butylene glycol, and mixtures thereof. 31. The method of claim 29, wherein the polyol is a mixture of polyethylene glycol and propylene glycol. 32. The method of claim 31, wherein the weight ratio of the polyethylene glycol to the propylene glycol is about 3:1. D. The method of claim 25, wherein the composition comprises an antioxidant in an amount effective to prevent degradation of the polyol. The method of claim 33, wherein the antioxidant is selected from the group consisting of tocopherol, ascorbic acid, and butylated hydroxyindole (BHT), and the polyol is selected from the group consisting of propylene glycol and poly A group of ethylene glycol, butyl diol, hexane diol, and combinations thereof. The method of claim 33, wherein the antioxidant is present in an amount of from about 0.05% to about 3% by weight. 36. The method of claim 35, wherein the antioxidant is selected from the group consisting of alpha-tocopherol, alpha-tocopherol acetate, and mixtures thereof. 37. The method of claim 25, wherein the composition comprises an effective amount of at least one sensitizer. The method of claim 37, wherein the sensitizer is present in the range of from about 0.05 to about 5% by weight. 39. The method of claim 37, wherein the sensitizer is selected from the group consisting of a cooling compound, a warming compound, a pungent compound, and mixtures thereof. The method of claim 39, wherein the cooling compound is selected from the group consisting of 2-isopropyl-N,2,3-trimercaptobutylamine, N-ethyl-p-capane-3 - Carboxylamamine and ethyl 3-(p-cappedo-3-carboxyguanidino) acetate menthone glycerol ketal, (-)-lactic acid capping, (-)-isomethampin, α-glucose Base orange 5 citrus and its mixture. 41. The method of claim 39, wherein the warming compound is selected from the group consisting of piperine, 1-ethoxylated piperonyl acetate, alpha-hydroxy shansool, Timurol, orange peel, ginger extract, and Its mixture. 42. The method of claim 39, wherein the pungent compound is selected from the group consisting of Shansools, Golden Button Alcohol, Timurol, and mixtures thereof. 43. The method of claim 25, wherein the composition comprises an effective Amount of lubricant and viscosity agent. The method of claim 43, wherein the lubricant is selected from the group consisting of carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl fluorenyl fiber, hydroxypropyl cellulose, and mixtures thereof. Group of. 45. The method of claim 43, wherein the lubricant is present in an amount from about D 0.05 to about 5% by weight. 46. The method of claim 25, wherein the composition is non-moisturizing and wherein the increase in blood flow is less than 300%. The composition of claim 1, wherein the vasodilator is selected from the group consisting of an endogenous and exogenous vasodilator. 48. The composition of claim 47, wherein the vasodilator comprises an endogenous vasodilator selected from the group consisting of nitric oxide, group 57 200927109, amine, prostaglandin D2, adenosine, L-fine A group of amino acids and soothing kinins. 49. 50. 15 52. 15 The composition of claim 47, wherein the vasodilator comprises an exogenous vasodilator selected from the group consisting of a nitric oxide inducer and a PDE5 inhibitor Group. The composition of claim 49, wherein the exogenous vasodilator comprises a nitric oxide inducer' is selected from the group consisting of nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, and pentaerythritol. Group of nitrate (pentaerythritoltetranitrate) and nitroxonium ferricyanide. The composition of claim 49, wherein the exogenous vasodilator comprises a selected from the group consisting of sildenafii, tadalafil, vardenafil, caffeine (the br〇mine) and a sweetener. a ρ〇Ε5 inhibitor of the group of papaverine. The composition of claim 1, wherein the vasodilator is selected from the group consisting of a test brew and a test acid derivative. 58 200927109 IV. Designation of Representative Representatives: (1) The representative representative of the case is: (No). (2) A brief description of the component symbols of this representative figure: None 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: